1,2-Dimethoxyethane → 1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3'-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride

HRID 553509ノート

反応式

HRID 553509 の反応式
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.COCCOC.[C:33]([CH2:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)#[N:34].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.O.C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[C:33]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]4[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=4)(=[O:19])=[O:18])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:38][CH:37]=1)#[N:34]

参加物

9

反応物 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27733424-(Cyanomethyl)benzeneboronic acidHCID 866402031-Methyl-1H-pyrazole-4-sulfonic acid [2-(3'-chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-ethyl]-methyl-amide

生成物 1

HCID 673688301-Methyl-1H-pyrazole-4-sulfonic acid {2-[3'-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride収率 71%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 21534740N,N-Dimethylacetamide--water (1/1)溶媒

反応条件

温度
110 °C

実験手順

Dissolve 1-methyl-1H-pyrazole-4-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide (0.250 g, 0.625 mmol) in DMA-H2O (or DME:H2O) (6 mL; 3:1 v/v, previously degassed with nitrogen). Add 4-cyanomethylphenyl boronic acid (0.121 g, 0.750 mmol), potassium carbonate (0.207 g, 1.500 mmol) and tetrakis(triphenylphosphine)palladium (0.036 g, 0.031 mmol). Stir the reaction mixture at 110° C. for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol. Purify by silica gel chromatography eluting with hexanes:acetone 1:1 to afford the free base of the title compound (0.214 g, 71% yield).

後処理

  1. custom3:1 v/v, previously degassed with nitrogen)
  2. temperatureCool
  3. extractionExtract the aqueous layer with ethyl acetate
  4. dry with materialDry the combined organic layers over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by SCX chromatography
  8. washeluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol
  9. customPurify by silica gel chromatography
  10. washeluting with hexanes:acetone 1:1

出典と根拠

ORDレコード
ord-acf2e4662d2345d7b20de649db1d2f69
出典データセット
uspto-grants-2011_11
特許番号
US08048884B2

反応ノート

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